Ventricular fibrillation resulting from contrast media during coronary arteriography has been observed to occur in approximately 8% of clinical procedures. Although this risk is not as significant as the risk of infarction it is still worthy of concern. In the proposed study we will investigate the contribution of a number of factors to the risk of ventricular fibrillation. These factors include: calcium ion complexing agents found in present contrast media, pre-treatment with cardiac glycosides, and chronic ischemic heart disease. It addition we will obtain some basic information concerning the effects of contrast media and calcium ion complexing agents on cell water and electrolyte balances. The various factors we hypothesize as promoting fibrillation will be investigated using a dog model. Controlled injections of media containing the complexing agents or supplemental calcium will be made into the dog right coronary artery using a procedure which we have shown produces a high incidence of fibrillation. Coronary sinus blood will be collected and analyzed for calcium ion concentration and other parameters. In vitro studies will be performed to demonstrate that the complexing of calcium ions is rapid enough to be of consequence in arteriography and that there is also a change in cell water, electrolytes, and membrane potential. In another series of experiments the dogs will be pre-treated with cardiac glycosides to determine if there is a synergism between the glycosides and contrast media in the production of fibrillation during coronary arteriography. We have already found such a synergism in mice given large intravenous doses of contrast media. Ischemic heart disease will be produced in dogs by inserting a polyethylene tube into the coronary artery under fluoroscopic control. After 7 to 14 days of recovery coronary arteriography will then be performed. This technique for producing ischemic heart disease has already been used successfully in our laboratory. We expect that the ischemic state will result in an increased incidence of fibrillation.